SynthesisGenetic epidemiology2014
A method for gene-based pathway analysis using genomewide association study summary statistics reveals nine new type 1 diabetes associations.
Synthesis in Genetic epidemiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations.PLoS genetics · 2016Pooled it
- Lnk/Sh2b3 regulates initiation and severity of autoimmune insulitis and contributes to diabetes risk.Life science alliance · 2025Article
- Type 1 Diabetes Genetics Consortium.The Journal of clinical endocrinology and metabolism · 2025Review
- A regulatory variant rs9379874 in T1D risk region 6p22.2 affects BTN3A1 expression regulating T cell function.Acta diabetologica · 2025Article
- Linking epigenetic mechanisms of T cell dysfunction with pathophysiology of type 1 diabetes mellitus.Frontiers in immunology · 2025Review
- Interleukin-27 and Autoimmune Disorders: A Compressive Review of Immunological Functions.Biomolecules · 2024Review
- Network propagation for GWAS analysis: a practical guide to leveraging molecular networks for disease gene discovery.Briefings in bioinformatics · 2024Review
- Gene-environment interaction in the pathophysiology of type 1 diabetes.Frontiers in endocrinology · 2024Article
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- Longitudinal DNA methylation profiling of the rectal mucosa identifies cell-specific signatures of disease status, severity and clinical outcomes in ulcerative colitis cell-specific DNA methylation signatures of UC.Clinical epigenetics · 2023Article
- A comprehensive comparison of multilocus association methods with summary statistics in genome-wide association studies.BMC bioinformatics · 2022Article
- NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes.Cell death & disease · 2022Article
- Article
- Self-Renewing Islet TCF1Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Multifactorial Progression from the Islet Autoimmunity to Type 1 Diabetes in Children.International journal of molecular sciences · 2021Review
- Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes.Nature genetics · 2021Article
- Article
- Activation of NF-κB-Inducing Kinase in Islet β Cells Causes β Cell Failure and Diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Genetics of fulminant type 1 diabetes.Diabetology international · 2020Review
- CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Pathway analysis can complement point-wise single nucleotide polymorphism (SNP) analysis in exploring genomewide association study (GWAS) data to identify specific disease-associated genes that can be candidate causal genes. We propose a straightforward methodology that can be used for conducting a gene-based pathway analysis using summary GWAS statistics in combination with widely available reference genotype data. We used this method to perform a gene-based pathway analysis of a type 1 diabetes (T1D) meta-analysis GWAS (of 7,514 cases and 9,045 controls). An important feature of the conducted analysis is the removal of the major histocompatibility complex gene region, the major genetic risk factor for T1D. Thirty-one of the 1,583 (2%) tested pathways were identified to be enriched for association with T1D at a 5% false discovery rate. We analyzed these 31 pathways and their genes to identify SNPs in or near these pathway genes that showed potentially novel association with T1D and attempted to replicate the association of 22 SNPs in additional samples. Replication P-values were skewed (P=9.85×10-11) with 12 of the 22 SNPs showing P<0.05. Support, including replication evidence, was obtained for nine T1D associated variants in genes ITGB7 (rs11170466, P=7.86×10-9), NRP1 (rs722988, 4.88×10-8), BAD (rs694739, 2.37×10-7), CTSB (rs1296023, 2.79×10-7), FYN (rs11964650, P=5.60×10-7), UBE2G1 (rs9906760, 5.08×10-7), MAP3K14 (rs17759555, 9.67×10-7), ITGB1 (rs1557150, 1.93×10-6), and IL7R (rs1445898, 2.76×10-6). The proposed methodology can be applied to other GWAS datasets for which only summary level data are available.
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Registered trials
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